Unusual effects of (rs505151) variation in patients with in-stent restenosis: Variable effects on restenosis risk according to concomitant chronic conditions.

Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function (rs505151) mutation of the gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of ( < 0.05), hyperlipidemia (HL) ( < 0.001), and type 2 diabetes (T2DM) ( < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the -G allele was associated with hypercholesterolemia and a higher risk of ISR ( < 0.001), while the AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels ( < 0.05) and the -AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the variation may be involved in the risk of ISR in association with concomitant metabolic diseases.